PPIs, H2 blockers not linked to cognitive problems in older patients, study finds
Data from a post hoc analysis of a randomized trial should provide reassurance about the safety of long-term use of proton-pump inhibitors (PPIs) among adults ages 65 years and older, according to the authors.
Proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists were not associated with incident dementia, cognitive impairment, or decline in cognition in older adults, a study found.
Researchers conducted a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia that enrolled 18,934 community-based adults ages 65 years and older from 2010 to 2014. Patients did not have cardiovascular disease, dementia, or physical disability at the start of the trial and were expected to survive for at least five years; they scored higher than 78 on the baseline Modified Mini-Mental State Examination (3MS) and were invited to participate in the ASPREE-eXTension study, an ongoing observational study, after the main trial ended.
The researchers determined PPI and H2 blocker use by review of medications during annual in-person study visits and defined incident dementia according to DSM-IV criteria. Secondary end points included cognitive impairment without dementia and changes in cognition. The researchers examined associations of medication use with dementia and cognitive impairment, as well as cognitive test scores. Results were published June 11 by Gastroenterology.
The study included 18,934 patients, 4,667 (24.6%) who took PPIs and 368 (1.9%) who took H2 blockers. In ASPREE, there were 572 cases of dementia (probable Alzheimer's disease, n=238; mixed presentations, n=334) during 84,995 person-years of follow-up (median, 4.5 years per person). There was no association between PPI use and risk for dementia (hazard ratio [HR], 0.88; 95% CI, 0.72 to 1.08), probable Alzheimer's disease (HR, 0.82; 95% CI, 0.59 to 1.14), or mixed presentations of dementia (HR, 0.93; 95% CI, 0.71 to 1.21) after adjustment for age, sex, years of education, country, race/ethnicity, smoking status, alcohol consumption, body mass index, family history of dementia, chronic kidney disease, type 2 diabetes, hypertension, depression score, baseline cognition, randomized trial intervention (aspirin or placebo), and the most common concomitant medications (antihypertensives, analgesics, and lipid-modifying agents). Similarly, there were no associations between H2 blocker use and dementia or cognitive impairment without dementia. The researchers also looked at data collected during additional follow-up of 120,194 person-years (median, 6.3 years per person) and found 861 incident cases of dementia but no association between baseline PPI use and dementia risk (HR, 0.91; 95% CI, 0.78 to 1.07).
These findings should reassure older adults and their clinicians about using PPIs, the authors concluded. They noted that links between PPIs and dementia in previous studies have been limited by confounding and may reflect PPI use as a marker of polypharmacy and comorbidity. “Given the high co-occurrence of combined use of PPIs with anti-hypertensive agents and lipid lowering agents in our cohort, PPI use could be a surrogate for cardiovascular disease, which is well-known to be linked with adverse cognitive outcomes,” they wrote.